This project will study the pathogenesis, diagnosis, and therapy of endogenous Candida and Aspergillus endophthalmitis in the rabbit and subhuman primate. Our investigations have demonstrated that progressive endophthalmitis can be produced by intravenous injection of C. albicans in rabbits. The incidence and severity of ocular infection and disseminated candidiasis are directly related to the species, strain, phase, and inoculum size of the organism. Intravenous amphotericin B, intravenous amphotericin B methyl ester, and oral ketoconazole reduce the severity of C. albicans endophthalmitis when initiated 7 days following inoculation and continued for 28 days. The efficacy of various other antibiotics and other routes of administration will be assessed in the rabbit and subhuman primate. The safety and efficacy of intravitreal antibiotics in the subhuman primate will be defined. The effects of corticosteroid and immunosuppressive therapy on the natural and treated disease will be determined. Similar methods will be utilized to study the pathogenesis and therapy of endogenous Aspergillus endophthalmitis. The results of these studies should amplify our understanding of the pathogenesis of ocular fungi and have direct application to the diagnosis and therapy of varous forms of fungal endophthalmitis and disseminated infection.